ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans

Hingley-Wilson, Suzanne M., Connell, David, Pollock, Katrina, Hsu, Tsungda, Tchilian, Elma, Sykes, Anny, Grass, Lisa, Potiphar, Lee, Bremang, Samuel, Kon, Onn Min, Jacobs, William R. and Lalvani, Ajit (2014) ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans. Tuberculosis, 94 (3). pp. 262-270. doi:10.1016/j.tube.2014.01.004

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Abstract

Mycobacterium tuberculosis-induced cellular aggregation is essential for granuloma formation and may assist establishment and early spread of M. tuberculosis infection. The M. tuberculosis ESX1 mutant, which has a non-functional type VII secretion system, induced significantly less production of the host macrophage-derived chemokine fractalkine (CX3CL1). Upon infection of human macrophages ESX1dependent fractalkine production mediated selective recruitment of CD11bþ monocytic cells and increased infection of neighbouring cells consistent with early local spread of infection. Fractalkine levels were raised in vivo at tuberculous disease sites in humans and were significantly associated with increased CD11bþ monocytic cellular recruitment and extent of granulomatous disease. These findings suggest a novel fractalkine-dependent ESX1-mediated mechanism in early tuberculous disease pathogenesis in humans. Modulation of M. tuberculosis-mediated fractalkine induction may represent a potential treatment option in the future, perhaps allowing us to switch off a key mechanism required by the pathogen to spread between cells.

Item Type:	Article
Article Type:	Article
Uncontrolled Keywords:	ESX-1; Fractalkine; Infection; Mycobacterium; Tuberculosis
Subjects:	R Medicine > RC Internal medicine
Divisions:	Schools and Research Institutes > School of Health and Social Care
Research Priority Areas:	Health, Life Sciences, Sport and Wellbeing
Depositing User:	Marta Kemp
Date Deposited:	11 Feb 2020 13:55
Last Modified:	27 Jul 2023 15:33
URI:	https://eprints.glos.ac.uk/id/eprint/8149

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